In-school adolescents' sociodemographic correlates of serious unintentional injuries in Saint Vincent and the Grenadines: A cross-sectional study.

Background: As a public health concern, serious adolescent injuries constitute considerable global morbidity and mortality. Despite the proliferation of literature on this problem, the evidence on the determinants of injuries among in-school adolescents in Saint Vincent and the Grenadines (SVG) is insufficient. Method: The study analyzed data from the 2018 Global School-based Student Health Survey to examine the prevalence and determinants of serious injuries in a nationwide adolescent sample in SVG. χ 2 And binomial logistic regression analyses were carried out, along with an adjusted odds ratio and a 95% confidence interval. Results: Serious injuries among this population were estimated at 50.5%. Student grades, gender, truancy, amphetamine or methamphetamine use, marijuana or alcohol use, cigarette smoking, physical assault, physical fight, cyberbullying, suicidal behavior (ideation, plan, and attempt), parental or guardian tobacco use, and multiple sexual partners were significantly associated with serious injuries. After adjusting for other variables, being a male, having experienced a physical attack, fighting physically, attempting suicide, and having multiple sexual partners predicted serious injuries among in-school adolescents in SVG. Conclusion: The use of integrative health promotion and injury prevention programmes (e.g., antiviolence campaigns) and educational measures could help minimize or eradicate this menace in SVG.

Utilisation of goals of care discussions and palliative care prior to image-guided procedures near the end of life.

AIM: To characterise image-guided procedures performed near the end of life and the use of goals of care discussions (GOC) and palliative care consultation (PCC) prior to these procedures. MATERIALS AND METHODS: Retrospective chart review of 3,714 consecutive inpatient procedures performed for 2,351 patients and 8,206 outpatient procedures performed for 5,225 patients within a suburban medical system. Data were collected on demographics, procedures performed, mortality, and use of GOC or PCC prior to the procedures. Procedures near the end of life were classified as emergent, elective, or palliative. Logistic regression was used to assess for demographic disparities in care. RESULTS: Nine percent of inpatients died within 30 days of their procedure, 57% of which were within the same hospitalisation. Of these patients, 59% had a documented GOC and 35% had a PCC. Similarly, 7% of outpatients died within 6 months of their procedure. A minority of these patients had a documented GOC (37%) or PCC (13%). There were few statistically significant demographic disparities in this care and the associated odds ratios were small. CONCLUSION: A wide array of image-guided procedures is performed near the end of life. GOC and PCC are underutilised prior to these procedures. Few demographic disparities exist in this care.

A mathematical study on a fractional COVID-19 transmission model within the framework of nonsingular and nonlocal kernel.

In this work, a mathematical model consisting of a compartmentalized coupled nonlinear system of fractional order differential equations describing the transmission dynamics of COVID-19 is studied. The fractional derivative is taken in the Atangana-Baleanu-Caputo sense. The basic dynamic properties of the fractional model such as invariant region, existence of equilibrium points as well as basic reproduction number are briefly discussed. Qualitative results on the existence and uniqueness of solutions via a fixed point argument as well as stability of the model solutions in the sense of Ulam-Hyers are furnished. Furthermore, the model is fitted to the COVID-19 data circulated by Nigeria Centre for Disease Control and the two-step Adams-Bashforth method incorporating the noninteger order parameter is used to obtain an iterative scheme from which numerical results for the model can be generated. Numerical simulations for the proposed model using Adams-Bashforth iterative scheme are presented to describe the behaviors at distinct values of the fractional index parameter for of each of the system state variables. It was shown numerically that the value of fractional index parameter has a significant effect on the transmission behavior of the disease however, the infected population (the exposed, the asymptomatic infectious, the symptomatic infectious) shrinks with time when the basic reproduction number is less than one irrespective of the value of fractional index parameter.

Increased variability in Apc(Min)/+ intestinal tissue can be measured with microultrasound.

Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic.

Opposing actions of the synapse-associated protein of 97-kDa molecular weight (SAP97) and Disrupted in Schizophrenia 1 (DISC1) on Wnt/ß-catenin signaling.

It has been suggested that synapse-associated protein of 97-kDa molecular weight (SAP97) is a susceptibility factor for childhood and adult neuropsychiatric disorders. SAP97 is a scaffolding protein that shares direct and indirect binding partners with the Disrupted in Schizophrenia 1 (DISC1) gene product, a gene with strong association with neuropsychiatric disorders. Here we investigated the possibility that these two proteins converge upon a common molecular pathway. Since DISC1 modifies Wnt/ß-catenin signaling via changes in glycogen synthase kinase 3 beta (GSK3ß) phosphorylation, we asked if SAP97 impacts Wnt/ß-catenin signaling and GSK3ß phosphorylation. We find that SAP97 acts as inhibitor of Wnt signaling activity and can suppress the stimulatory effects of DISC1 on ß-catenin transcriptional activity. Reductions in SAP97 abundance also decrease GSK3ß phosphorylation. In addition, we find that over expression of DISC1 leads to an increase in the abundance of SAP97, by inhibiting its proteasomal degradation. Our findings suggest that SAP97 and DISC1 contribute to maintaining Wnt/ß-catenin signaling activity within a homeostatic range by regulating GSK3ß phosphorylation.

Interactions between Cooccurring Lactic Acid Bacteria in Honey Bee Hives.

In contrast to the honey bee gut, which is colonized by a few characteristic bacterial clades, the hive of the honey bee is home to a diverse array of microbes, including many lactic acid bacteria (LAB). In this study, we used culture, combined with sequencing, to sample the LAB communities found across hive environments. Specifically, we sought to use network analysis to identify microbial hubs sharing nearly identical operational taxonomic units, evidence which may indicate cooccurrence of bacteria between environments. In the process, we identified interactions between noncore bacterial members (Fructobacillus and Lactobacillaceae) and honey bee-specific "core" members. Both Fructobacillus and Lactobacillaceae colonize brood cells, bee bread, and nectar and may serve the role of pioneering species, establishing an environment conducive to the inoculation by honey bee core bacteria. Coculture assays showed that these noncore bacterial members promote the growth of honey bee-specific bacterial species. Specifically, Fructobacillus by-products in spent medium supported the growth of the Firm-5 honey bee-specific clade in vitro. Metabolic characterization of Fructobacillus using carbohydrate utilization assays revealed that this strain is capable of utilizing the simple sugars fructose and glucose, as well as the complex plant carbohydrate lignin. We tested Fructobacillus for antibiotic sensitivity and found that this bacterium, which may be important for establishment of the microbiome, is sensitive to the commonly used antibiotic tetracycline. Our results point to the possible significance of "noncore" and environmental microbial community members in the modulation of honey bee microbiome dynamics and suggest that tetracycline use by beekeepers should be limited.

Development of methods for cross-sectional HIV incidence estimation in a large, community randomized trial.

BACKGROUND: Accurate methods of HIV incidence determination are critically needed to monitor the epidemic and determine the population level impact of prevention trials. One such trial, Project Accept, a Phase III, community-randomized trial, evaluated the impact of enhanced, community-based voluntary counseling and testing on population-level HIV incidence. The primary endpoint of the trial was based on a single, cross-sectional, post-intervention HIV incidence assessment. METHODS AND FINDINGS: Test performance of HIV incidence determination was evaluated for 403 multi-assay algorithms [MAAs] that included the BED capture immunoassay [BED-CEIA] alone, an avidity assay alone, and combinations of these assays at different cutoff values with and without CD4 and viral load testing on samples from seven African cohorts (5,325 samples from 3,436 individuals with known duration of HIV infection [1 month to >10 years]). The mean window period (average time individuals appear positive for a given algorithm) and performance in estimating an incidence estimate (in terms of bias and variance) of these MAAs were evaluated in three simulated epidemic scenarios (stable, emerging and waning). The power of different test methods to detect a 35% reduction in incidence in the matched communities of Project Accept was also assessed. A MAA was identified that included BED-CEIA, the avidity assay, CD4 cell count, and viral load that had a window period of 259 days, accurately estimated HIV incidence in all three epidemic settings and provided sufficient power to detect an intervention effect in Project Accept. CONCLUSIONS: In a Southern African setting, HIV incidence estimates and intervention effects can be accurately estimated from cross-sectional surveys using a MAA. The improved accuracy in cross-sectional incidence testing that a MAA provides is a powerful tool for HIV surveillance and program evaluation.

Antibody maturation and viral diversification in HIV-infected women.

INTRODUCTION: The Post-exposure Prophylaxis in Infants (PEPI)-Malawi trial evaluated infant antiretroviral regimens for prevention of post-natal HIV transmission. A multi-assay algorithm (MAA) that includes the BED capture immunoassay, an avidity assay, CD4 cell count, and viral load was used to identify women who were vs. were not recently infected at the time of enrollment (MAA recent, N = 73; MAA non-recent, N = 2,488); a subset of the women in the MAA non-recent group known to have been HIV infected for at least 2 years before enrollment (known non-recent, N = 54). Antibody maturation and viral diversification were examined in these women. METHODS: Samples collected at enrollment (N = 2,561) and 12-24 months later (N = 1,306) were available for serologic analysis using the BED and avidity assays. A subset of those samples was used for analysis of viral diversity, which was performed using a high resolution melting (HRM) diversity assay. Viral diversity analysis was performed using all available samples from women in the MAA recent group (61 enrollment samples, 38 follow-up samples) and the known non-recent group (43 enrollment samples, 22 follow-up samples). Diversity data from PEPI-Malawi were also compared to similar data from 169 adults in the United States (US) with known recent infection (N = 102) and known non-recent infection (N = 67). RESULTS: In PEPI-Malawi, results from the BED and avidity assays increased over time in the MAA recent group, but did not change significantly in the MAA non-recent group. At enrollment, HIV diversity was lower in the MAA recent group than in the known non-recent group. HRM diversity assay results from women in PEPI-Malawi were similar to those from adults in the US with known duration of HIV infection. CONCLUSIONS: Antibody maturation and HIV diversification patterns in African women provide additional support for use of the MAA to identify populations with recent HIV infection.

Vitamin D levels in Malawian infants from birth to 24 months.

We measured longitudinal levels of vitamin D in unsupplemented Malawian infants at 0 (birth), 2, 12, 15, 18 and 24 months of age. Matched maternal plasma and breast milk vitamin D(2) and D(3) levels were also measured at delivery and 2 months postpartum. Vitamin D was measured using isotope-dilution liquid chromatography tandem-mass spectrometry. Vitamin D(3) levels in children were 36% of adult levels at birth, 60% of adult levels at age 2 months, and at par with adult levels by 12 months of age. This adult-equivalent level is subsequently maintained through age 24 months and consisted of a 98% molar ratio of vitamin D(3). Vitamin D levels in breast milk were below the limit of detection, 0.1 ng/ml. Breast milk of unsupplemented Malawian mothers is a poor source of vitamin D.

Distribution of haematological and chemical pathology values among infants in Malawi and Uganda.

BACKGROUND: Data on paediatric reference laboratory values are limited for sub-Saharan Africa. OBJECTIVE: To describe the distribution of haematological and chemical pathology values among healthy infants from Malawi and Uganda. METHODS: A cross-sectional study was conducted among healthy infants, 0-6 months old, born to HIV-uninfected mothers recruited from two settings in Blantyre, Malawi and Kampala, Uganda. Chemical pathology and haematology parameters were determined using standard methods on blood samples. Descriptive analyses by age-group were performed based on 2004 Division of AIDS Toxicity Table age categories. Mean values and interquartile ranges were compared by site and age-group. RESULTS: A total of 541 infants were included altogether, 294 from Malawi and 247 from Uganda. Overall, the mean laboratory values were comparable between the two sites. Mean alkaline phosphatase levels were lower among infants aged ≤21 days while aspartate aminotransferase, creatinine, total bilirubin and gamma-glutamyl transferase were higher in those aged 0-7 days than in older infants. Mean haematocrit, haemoglobin and neutrophil counts were higher in the younger age-groups (<35 days) and overall were lower than US norms. Red and white blood cell counts tended to decrease after birth but increased after ∼2 months of age. Mean basophil counts were higher in Malawi than in Uganda in infants aged 0-1 and 2-7 days; mean counts for eosinophils (for age groups 8-21 or older) and platelets (for all age groups) were higher in Ugandan than in Malawian infants. Absolute lymphocyte counts increased with infant age. CONCLUSION: The chemical pathology and haematological values in healthy infants born to HIV-uninfected mothers were comparable in Malawi and Uganda and can serve as useful reference values in these settings.

Stavudine concentrations in women receiving postpartum antiretroviral treatment and their breastfeeding infants.

First-line antiretroviral treatment regimens in resource-limited settings used in breastfeeding mothers often include stavudine (d4T). Limited data describing d4T concentrations in breast milk are available. We analyzed d4T concentrations in 52 mother-infant pairs using ultra-performance liquid chromatography-tandem mass spectrometry (lower limit of quantification: 5 ng/mL in plasma, 20 ng/mL in breast milk). Median (interquartile range) d4T concentrations were 86 (36-191) ng/mL in maternal plasma, 151 (48-259) ng/mL in whole milk, 190 (58-296) ng/mL in skim milk, and <5 (<5 to <5) ng/mL in infant plasma. Although d4T is concentrated in breast milk relative to maternal plasma, the infant d4T dose received from breast milk is very small and not clinically significant.

Trends in birth weight and gestational age for infants born to HIV-infected, antiretroviral treatment-naive women in Malawi.

BACKGROUND: We analyzed birth outcomes among infants of treatment-naive, HIV-infected women from a series of mother-to-child transmission of HIV studies in Blantyre, Malawi. METHODS: Data from 6 prospective studies at 1 research site were analyzed. Mean birth weight (BW) and gestational age (GA), and frequency of low birth weight (LBW; <2500 g) and preterm (PT) birth (GA < 37 weeks) were estimated. We assessed risk factors for LBW and PT birth using mixed-effects logistic regression. Adjusted odds ratios (AOR) and 95% confidence intervals from earlier studies (1989-1994) and later studies (2000-2007) are presented separately. RESULTS: The analysis included 8874 HIV-exposed infants. Mean BW and GA ranged from 2793 to 3079 g, and from 37.8 to 39.0 weeks. Greater maternal age was consistently (during both the early and late periods) associated with lower odds of LBW and PT birth; AOR (95% confidence intervals) for both outcomes in the early and late periods, respectively, were 0.98 (0.96-1.00) and 0.97 (0.95-0.99). Female infant gender was consistently associated with higher odds of PT birth during both periods and with higher odds of LBW during the later period. During the early period, higher maternal education was associated with lower odds of LBW (AOR 0.67 [0.48-0.95]) and PT birth (AOR 0.70 [0.51-0.95]), and later birth year was associated with lower odds of PT birth (AOR 0.35 [0.19-0.70]). CONCLUSIONS: BW and GA remained stable within each time period. This analysis provides important baseline information for monitoring HIV treatment effects on birth outcomes. Modifiable factors affecting BW and GA should continue to be explored.

Effects of cessation of breastfeeding in HIV-1-exposed, uninfected children in Malawi.

BACKGROUND: We assessed morbidity rates during short intervals that accompanied weaning and cumulative mortality among HIV-exposed, uninfected infants enrolled in the postexposure prophylaxis of infants in Malawi (PEPI-Malawi) trial. METHODS: Women were counseled to stop breastfeeding (BF) by 6 months in the PEPI-Malawi trial. HIV-uninfected infants were included in this analysis starting at age 6 months. Breastfeeding and morbidity (illness and/or hospital admission and malnutrition [weight-for-age Z-score, ≤2]) were assessed during age intervals of 6-9, 9-12, and 12-15 months. BF was defined as any BF at the start and end of the interval and no breastfeeding (NBF) was defined as NBF at any time during the interval. The association of NBF with morbidity at each mutually exclusive interval was assessed using Poisson regression models controlling for other factors. Cumulative mortality among infants aged 6-15 months with BF and NBF was assessed using an extended Kaplan-Meier method. RESULTS: At age 6 months, 1761 HIV-uninfected infants were included in the study. The adjusted rate ratios for illnesses and/or hospital admission for NBF, compared with BF, was 1.7 (P < .0001) at 6-9 months, 1.66 (P = .0001) at 9-12 months, and 1.75 (P = .0008) at 12-15 months. The rates of morbidity were consistently higher among NBF infants during each age interval, compared with BF infants. The 15 months cumulative mortality among BF and NBF children was 3.5% and 6.4% (P = .03), respectively. CONCLUSIONS: Cessation of BF is associated with acute morbidity events and cumulative mortality. Prolonged BF should be encouraged, in addition to close monitoring of infant health and provision of support services.

Association of recent HIV infection and in-utero HIV-1 transmission.

OBJECTIVE: We previously developed a multiassay algorithm (MAA) to identify recent HIV infection that includes the BED-capture enzyme immunoassay, an avidity assay based on the Genetic Systems HIV-1/HIV-2 + O enzyme immunoassay, CD4 cell count, and HIV viral load. We used this MAA to evaluate the association between recent maternal HIV infection and in-utero transmission of HIV. METHODS: Plasma samples were collected at delivery from 2561 HIV-infected women in the postexposure prophylaxis of infants-Malawi trial. The MAA described above was used to identify women with recent HIV infection. Logistic regression models assessed association between recent HIV infection and in-utero HIV transmission (defined as a positive infant HIV DNA test at birth). RESULTS: Seventy-three women were identified as recently infected using the MAA. Those women were younger and had lower parity than women who were identified as not recently infected using the MAA (P < 0.0001 for age and parity). The frequency of in-utero HIV transmission was 17.8% among women identified as recently infected, compared with 6.7% among women identified as not recently infected (13/73 vs. 166/2488, P = 0.001). In a multivariate model, three factors were independently associated with in-utero HIV transmission: recent infection [adjusted odds ratio (AOR): 2.49, 95% confidence interval (CI): 1.30-4.78, P = 0.006], log(10) HIV viral load at delivery (AOR: 2.01, 95% CI: 1.60-2.51, P < 0.0001), and younger age (per 10 year increase, AOR: 0.66, 95% CI: 0.43-0.93, P = 0.02). CONCLUSION: Results obtained using a MAA suggest that recent maternal HIV acquisition is strongly associated with in-utero HIV transmission, independent of HIV viral load at delivery.

Initiation of antiretroviral treatment in women after delivery can induce multiclass drug resistance in breastfeeding HIV-infected infants.

BACKGROUND: The World Health Organization currently recommends initiation of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)-infected lactating women with CD4+ cell counts <350 cells/µL or stage 3 or 4 disease. We analyzed antiretroviral drug resistance in HIV-infected infants in the Post Exposure Prophylaxis of Infants trial whose mothers initiated HAART postpartum (with a regimen of nevirapine [NVP], stavudine, and lamivudine). Infants in the trial received single-dose NVP and a week of zidovudine (ZDV) at birth; some infants also received extended daily NVP prophylaxis, with or without extended ZDV prophylaxis. METHODS: We analyzed drug resistance in plasma samples collected from all HIV-infected infants whose mothers started HAART in the first postpartum year. Resistance testing was performed using the first plasma sample collected within 6 months after maternal HAART initiation. Categorical variables were compared by exact or trend tests; continuous variables were compared using rank-sum tests. RESULTS: Multiclass resistance (MCR) was detected in HIV from 11 (29.7%) of 37 infants. Infants were more likely to develop MCR infection if their mothers initiated HAART earlier in the postpartum period (by 14 weeks vs after 14 weeks and up to 6 months vs after 6 months, P = .0009), or if the mother was exclusively breastfeeding at the time of HAART initiation (exclusive breastfeeding vs mixed feeding vs no breastfeeding, P = .003). CONCLUSIONS: Postpartum maternal HAART initiation was associated with acquisition of MCR in HIV-infected breastfeeding infants. The risk was higher among infants whose mothers initiated HAART closer to the time of delivery or were still exclusively breastfeeding when they first reported HAART use.

Postexposure prophylaxis of breastfeeding HIV-exposed infants with antiretroviral drugs to age 14 weeks: updated efficacy results of the PEPI-Malawi trial.

BACKGROUND: This analysis updates and extends efficacy estimates of the PEPI-Malawi trial through age 24 months at study completion in September 2009. METHODS: Infants of breastfeeding HIV-infected women were randomized at birth to the following: (1) single-dose nevirapine (NVP) + 1-week zidovudine (ZDV) (control); (2) control + extended daily NVP (ExtNVP) through 14 weeks; (3) control + extended daily NVP + ZDV (ExtNVP/ZDV) through 14 weeks. We estimated rates of HIV infection, death and HIV infection, or death using Kaplan-Meier analysis. RESULTS: This analysis includes 3126 infants uninfected at birth as follows: 1004 control, 1071 ExtNVP, and 1051 ExtNVP/ZDV. By 9 months, HIV infection rates were 5.0% in ExtNVP, 6.0% in ExtNVP/ZDV, and 11.1% in control (P < 0.001 comparing extended regimens with control). At age 24 months, HIV infection rates had risen to ~11% in the extended arms compared with 15.6% in the controls (P < 0.05). The rates of HIV infection or death were also significantly lower in extended arms. There were no differences in severe adverse events with the exception of higher possibly related events in the ExtNVP/ZDV arm. CONCLUSIONS: Daily infant antiretroviral prophylaxis reduces postnatal HIV infection by ~70% during the period of prophylaxis. But continued HIV transmission after prophylaxis stops suggests more prolonged infant prophylaxis is needed.

Age-related synapse loss in hippocampal CA3 is not reversed by caloric restriction.

Caloric restriction (CR) is a reduction of total caloric intake without a decrease in micronutrients or a disproportionate reduction of any one dietary component. While CR attenuates age-related cognitive deficits in tasks of hippocampal-dependent memory, the cellular mechanisms by which CR improves this cognitive decline are poorly understood. Previously, we have reported age-related decreases in key synaptic proteins in the CA3 region of the hippocampus that are stabilized by lifelong CR. In the present study, we examined possible age-related changes in the functional microcircuitry of the synapses in the stratum lacunosum-molecular (SL-M) of the CA3 region of the hippocampus, and whether lifelong CR might prevent these age-related alterations. We used serial electron microscopy to reconstruct and classify SL-M synapses and their postsynaptic spines. We analyzed synapse number and size as well as spine surface area and volume in young (10 months) and old (29 months) ad libitum fed rats and in old rats that were calorically restricted from 4 months of age. We limited our analysis to SL-M because previous work demonstrated age-related decreases in synaptophysin confined to this specific layer and region of the hippocampus. The results revealed an age-related decrease in macular axo-spinous synapses that was not reversed by CR that occurred in the absence of changes in the size of synapses or spines. Thus, the benefits of CR for CA3 function and synaptic plasticity may involve other biological effects including the stabilization of synaptic proteins levels in the face of age-related synapse loss.

Frequency of gastroenteritis and gastroenteritis-associated mortality with early weaning in HIV-1-uninfected children born to HIV-infected women in Malawi.

BACKGROUND: We assessed gastroenteritis (GE) burden in 2 randomized trials conducted in Malawi to reduce postnatal HIV transmission before and after World Health Organization recommendations regarding exclusive breastfeeding for HIV-exposed infants were adopted. The 2 trials were the nevirapine/AZT (NVAZ, 2000-2003 with prolonged breastfeeding) and the Postexposure Prophylaxis to the Infant (PEPI, 2004-2007 with breastfeeding cessation by 6 months). METHODS: From NVAZ and PEPI trials data, GE frequency through age 12 months among HIV-negative exposed infants was evaluated. Overall and GE-related cumulative mortality rates were estimated using Kaplan-Meier curves. RESULTS: The frequency of at least one GE-related hospitalization was greater in PEPI vs. NVAZ after age 6 months (respectively, 2.9% vs. 0.1%, at 7-9 months and 1.6% vs. 0.2% at 10-12 months, P < 0.001). Cumulative GE-related mortality was significantly higher in PEPI than in NVAZ after age 6 months; at ages 9 and 12 months GE-related mortality was 19 and 24 per 1000 infants in PEPI vs. 7 and 12 per 1000 infants in NVAZ (P = 0.0002). CONCLUSIONS: Early weaning was associated with increased risk of severe GE and GE-related mortality among HIV-exposed infants. Strategies are urgently needed which allow longer breastfeeding while reducing the risk of HIV breast milk transmission in resource-limited settings.

Postnatal HIV-1 transmission after cessation of infant extended antiretroviral prophylaxis and effect of maternal highly active antiretroviral therapy.

BACKGROUND: The association between postnatal human immunodeficiency virus type 1 (HIV-1) transmission and maternal highly active antiretroviral therapy (HAART) after infant extended antiretroviral prophylaxis was assessed. METHODS: A follow-up study was conducted for the Post-Exposure Prophylaxis of Infants trial in Blantyre, Malawi (PEPI-Malawi). In PEPI-Malawi, breast-feeding infants of HIV-infected women were randomized at birth to receive a either control regimen (single-dose nevirapine plus 1 week of zidovudine); the control regimen plus nevirapine to age 14 weeks; or the control regimen plus nevirapine and zidovudine to age 14 weeks. Infant HIV infection, maternal CD4 cell count, and HAART use were determined. Maternal HAART use was categorized as HAART eligible but untreated (CD4 cell count of <250 cells/microL, no HAART received), HAART eligible and treated (CD4 cell count of <250 cells/microL, HAART received), and HAART ineligible (CD4 cell count of 250 cells/microL). The incidence of HIV infection and the association between postnatal HIV transmission and maternal HAART were calculated among infants who were HIV negative at 14 weeks. RESULTS: Of 2318 infants, 130 (5.6%) acquired HIV infection, and 310 mothers (13.4%) received HAART. The rates of HIV transmission (in cases per 100 person-years) were as follows: for the HAART-eligible/untreated category, 10.56 (95% confidence interval [CI], 7.91-13.82); for the HAART-eligible/treated category, 1.79 (95% CI, 0.58-4.18); and for the HAART-ineligible category, 3.66 (95% CI, 2.86-4.61). The HIV transmission rate ratio for the HAART-eligible/treated category versus the HAART-eligible/untreated category, adjusted for infant prophylaxis, was 0.18 (95% CI, 0.07-0.44). CONCLUSIONS: Postnatal HIV transmission continues after cessation of infant prophylaxis. HAART-eligible women should start treatment early for their own health and to reduce postnatal HIV transmission to their infants.

Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission.

BACKGROUND: Effective strategies are urgently needed to reduce mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding in resource-limited settings. METHODS: Women with HIV-1 infection who were breast-feeding infants were enrolled in a randomized, phase 3 trial in Blantyre, Malawi. At birth, the infants were randomly assigned to one of three regimens: single-dose nevirapine plus 1 week of zidovudine (control regimen) or the control regimen plus daily extended prophylaxis either with nevirapine (extended nevirapine) or with nevirapine plus zidovudine (extended dual prophylaxis) until the age of 14 weeks. Using Kaplan-Meier analyses, we assessed the risk of HIV-1 infection among infants who were HIV-1-negative on DNA polymerase-chain-reaction assay at birth. RESULTS: Among 3016 infants in the study, the control group had consistently higher rates of HIV-1 infection from the age of 6 weeks through 18 months. At 9 months, the estimated rate of HIV-1 infection (the primary end point) was 10.6% in the control group, as compared with 5.2% in the extended-nevirapine group (P<0.001) and 6.4% in the extended-dual-prophylaxis group (P=0.002). There were no significant differences between the two extended-prophylaxis groups. The frequency of breast-feeding did not differ significantly among the study groups. Infants receiving extended dual prophylaxis had a significant increase in the number of adverse events (primarily neutropenia) that were deemed to be possibly related to a study drug. CONCLUSIONS: Extended prophylaxis with nevirapine or with nevirapine and zidovudine for the first 14 weeks of life significantly reduced postnatal HIV-1 infection in 9-month-old infants. (ClinicalTrials.gov number, NCT00115648.)